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Entamoeba histolytica
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
William A. Petri, Jonathan I. Ravdin
Treatment of invasive amebiasis requires a combination of a well-absorbed drug to treat disease in the wall of the intestine and extraintestinally and a luminal drug to eliminate carriage of the amebas. Systemically absorbed antiamebic drugs include metronidazole, tinidazole (unavailable in the United States), emetine, and dehydroemetine (administered intramuscularly only), and chloroquine. Chloroquine has not been shown to be effective at treating intestinal disease and is reserved for amebic liver abscess not responding to metronidazole. Emetine and dehydroemetine are ipecac alkaloids that are not tolerated when given orally, have frequent cardiovascular side effects, and are also second-line drugs. Metronidazole is the drug of choice for invasive infection with E.. histolytica. A poorly absorbed antiamebic agent should be added to therapy with metronidazole (especially if the course is less than 10 days) to eliminate luminal E. histolytica; amebic liver abscess has occurred 1-3 months after treatment of amebic colitis with metronidazole alone (249). It is not clear when other agents should be added to metronidazole; patients with amebic liver abscess who fail metronidazole will usually respond to emetines plus chloroquine or require drainage (248). Metronidazole has been shown to be potentially both mutagenic and carcinogenic (250,251), and while the benefits of this drug outweigh the risks in treating invasive amebiasis, the ideal drug to treat amebiasis has yet to be found.
Treatment and Prevention of Amebiasis
Published in Roberto R. Kretschmer, Amebiasis: Infection and Disease by Entamoeba histolytica, 2020
The drug or the combination of drugs used to treat diseases caused by E. histolytica may vary depending on the reports that are consulted and trusted, and on the personal experience accumulated by the physician. The drug must be selected after careful evaluation of the patient, always keeping in mind possible contraindications. The most appropriate therapeutic strategies for each of the known leading clinical forms of amebiasis are as follows: Asymptomatic cyst carriers. These are defined as healthy individuals with E. histolytica cysts in their feces. The drug of choice is iodoquinol (Diodoquin®) for 20 days or paromomycin for 8 days. The concept of chronic colitis is still a matter of debate. Those who believe in it advocate a similar treatment as that recommended for asymptomatic cyst carriers.Acute amebic colitis (dysenteric syndrome). This syndrome is characterized by blood and mucus stained diarrhea and tenesmus. The recommended treatment is dehydro-emetine for 10 days plus metronidazole for 5 to 10 days. Some authors have reported good results with metronidazole alone. We prefer the combination of this drug with dehydroemetine. A possible alternative is iodoquinol plus dehydroemetine.Ameboma. The drugs of choice are dehydroemetine for 10 days followed by 10 days of metronidazole and then by iodoquinol for 20 days.Amebic liver abscess. The treatment is oral metronidazole for 10 days. Metronidazole is the most appropriate drug for patients with amebic liver abscess as shown in a study of 1998 patients.57 Some particularly severe cases may require a combined treatment with emetine. When the patient is malnourished, jaundiced, or does not tolerate oral administration of the drug, intravenous metronidazole is recommended at a dose of 500 mg every 6 to 8 hours for 10 days, plus intramuscular dehydroemetine.Amebiasis of the skin. Amebic skin lesions extend rapidly causing extensive necrosis. Treatment must therefore be prompt and vigorous. The drug of choice is dehydroemetine combined with metronidazole. If simultaneous bacterial infection is present antibiotics will be necessary. It is recommended that potassium permanganate be applied to the lesion at a 1:10,000 dilution.
Heat shock factor 1 (HSF1)-targeted anticancer therapeutics: overview of current preclinical progress
Published in Expert Opinion on Therapeutic Targets, 2019
Toshiki Kijima, Thomas Prince, Len Neckers, Fumitaka Koga, Yasuhisa Fujii
NZ28 and emunin, analogs of the general translational inhibitor dehydroemetine, are compounds screened from libraries of chemicals that potently inhibited HSP induction by heat shock, proteasome inhibitors, and HSP90 inhibitors [80]. At low micromolar concentrations, these compounds showed little acute toxicity, but sensitized myeloma and prostate carcinoma cells to the effects of HSP90 and proteasome inhibitors [80]. Synergistic effects of NZ28 with HSP90 inhibitors and radiation therapy were also shown in lung and breast cancer cells [81]. The precise target of NZ28 and emunin is unknown, but likely involves post-transcriptional events downstream of HSF1, thus raising specificity concerns.